Sample tray heater module

ABSTRACT

A heater module is described that includes a heat distribution plate including a bottom portion having first and second sides and a plurality of projections extending away from one of the sides. A heat source is provided for heating the heat distribution plate, and, optionally, a heating tray can be used to receive the heat source and heat distribution plate. The heater module is adapted to engage a sample purification tray having a plurality of purification and/or discharge columns which can extend through openings in the heater module and direct a sample into a sample receiving tray. Methods of heating samples using the heater module are also described.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part application of U.S.patent application Ser. No. 10/104,335, filed Mar. 22, 2002, which is acontinuation-in-part of U.S. patent application Ser. No. 09/552,301,filed Apr. 18, 2000, now U.S. Pat. No. 6,419,827 B1, issued Jul. 16,2002, which is a continuation-in-part of U.S. patent application Ser.No. 09/182,946, filed Oct. 29, 1998, now U.S. Pat. No. 6,159,368, issuedDec. 12, 2000. Cross reference is made to the following relatedapplications which are divisional applications of U.S. patentapplication Ser. No. 09/182,946 filed Oct. 29, 1998, now U.S. Pat. No.6,159,368, issued Dec. 12, 2000; U.S. patent application Ser. No.09/565,673, filed May 4, 2000, now U.S. Pat. No. 6,451,261 B1, issuedSep. 17, 2002; Ser. No. 09/565,202, filed May 4, 2000, now U.S. Pat. No.6,506,343 B1, issued Jan. 14, 2003; and Ser. No. 09/565,566 filed May 4,2000, now U.S. Pat. No. 6,338,802 B1, issued Jan. 15, 2002 Allreferences cited herein are incorporated in their entireties byreference.

FIELD

[0002] The present invention relates to a multi-well microfiltrationapparatus and methods for processing a plurality of fluid samplessimultaneously at a desired temperature.

BACKGROUND

[0003] In recent years, microtitration wells have assumed an importantrole in many biological and biochemical applications, such as samplepreparation, genome sequencing, and drug discovery programs. A varietyof multi-well arrangements, constructed according to standardizedformats, are now popular. Methods of heating samples in such multi-wellarrangements, such as those described in U.S. Pat. No. 5,459,300 andU.S. Pat. No. 5,681,492, are known in the art, but do not performconsistent, uniform heating of all samples in a multi-sample array.

[0004] It is desirable to provide an apparatus for consistently anduniformly maintaining, raising, or lowering the temperature of aplurality of samples, to facilitate processing such as purification.

SUMMARY

[0005] According to various embodiments, a sample tray heater modulethat can be used on an automated or manual sample preparation station isdescribed. According to various embodiments, the sample tray heatermodule can include a heat distribution plate and a heat source.According to various other embodiments, the sample tray heater modulecan further include a heating tray.

[0006] According to various embodiments, a system including a sampletray heater module is provided wherein the temperature of the sampletray heater module can be monitored and controlled during heating.According to various embodiments, the heater module is capable ofheating a sample to a temperature in a range of from about 5° C. toabout 100° C. In other embodiments, the heater module is capable ofheating a sample to a temperature in a range of from about 20° C. toabout 70° C. According to various embodiments, the heater module iscapable of heating a sample at a rate of greater than or equal to about1° C. per minute.

[0007] According to various embodiments, a system is provided wherein asample tray heater module can be fitted with a sample purification tray,and/or a receiving well array, prior to processing samples.

[0008] According to various embodiments, a sample tray heater module isprovided that includes a plurality of protrusions capable of interactingwith a sample purification tray for proper positioning thereof relativeto the heater module. The plurality of protrusions can provide uniformheating to a plurality of discharge columns of a sample purificationtray according to various embodiments.

[0009] According to various embodiments, a sample tray heater module isprovided that is inexpensive and reliable. According to variousembodiments, the sample tray heater module can be disposable. Accordingto various embodiments, the heat distribution plate, heat source, andoptional heating tray of the heater module can each be made from athermally conductive material such as a metal, metal alloy, or polymericmaterial, such as a thermoplastic, or a combination thereof.

[0010] A purification apparatus including a heater module for heating ofa sample passing therethrough is described according to variousembodiments.

[0011] According to various embodiments, a method is provided forpurifying a sample wherein the sample is heated during purification.

[0012] Additional features and advantages of the heater module and itsuse will be set forth in part in the description that follows, and inpart will be apparent from the description and drawings, or may belearned by practice. Objectives and other advantages of the heatermodule and methods of making and using the heater module will berealized and obtained by means of the elements and combinationsdescribed in the written description herein and the appended claims.

[0013] To achieve these and other advantages, a sample tray heatermodule is provided that includes a heat distribution plate and a heatsource. The heat distribution plate can include a bottom portion and oneor more protrusions extending away from the bottom portion. The heatsource can be in contact with an underside of the bottom portion of theheat distribution plate. One or more electrical contacts can be inelectrical communication with the heat source. Optionally, the heatermodule can include a heating tray adapted to receive the heat source andthe heat distribution plate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 is a perspective view of a sample purification tray and aheater module.

[0015]FIG. 2 is a top view of a heat distribution plate according tovarious embodiments.

[0016]FIG. 3 is a sectional side view taken along line 3-3 in FIG. 2.

[0017]FIG. 4 is a front view of a heater module according to variousembodiments.

[0018]FIG. 5 is a back view of the heater module shown in FIG. 4.

[0019]FIG. 6 is a bottom view of the heater module shown in FIGS. 4 and5.

[0020]FIG. 7 is a cut-away top view of a heater module according tovarious embodiments taken along various cut-aways.

[0021]FIG. 8 is a perspective view of a purification apparatus having asample purification tray, a heater module, and a sample well tray,wherein the heater module comprises a heat distribution plate, a heatsource, and a heating tray.

[0022]FIG. 9 is a side-sectional view of a heater module having aheating tray, a heat source, and a heat distribution plate.

[0023]FIG. 10 is a perspective view of a purification apparatusincluding a sample tray, a heater module, and a carriage.

[0024]FIG. 11 is a graph illustrating the temperature rate increase ofwater using a heater module according to various embodiments.

[0025] Other various embodiments of the present invention will beapparent to those skilled in the art from consideration of thespecification and practice of the invention described herein. It isintended that the specification and examples be considered as exemplaryonly, and that the true scope and spirit of the invention include thoseother various embodiments.

DESCRIPTION OF CERTAIN EMBODIMENTS

[0026] According to various embodiments, a sample tray heater module isprovided, for example, for a purification apparatus. The heater modulecan be used in or with an apparatus useful for purification, filtration,and/or separation of biological and/or chemical samples, such as DNA.The purification apparatus can include a sample purification tray havinga plurality of discharge columns, each with a distal end, wherein eachdischarge column is adapted to receive or includes a filter medium. Thesample purification tray can be, for example, a discharge conduit array,a sample purification array, or other device capable of receiving andallowing passage therethrough of a sample.

[0027] The sample purification tray can be disposed in a purificationapparatus and held aligned with and in fluid communication with areceiving well array, for example, a sample well array, sample welltray, sample tray, array of receiving wells, or other device capable ofreceiving and containing, restraining, or holding a sample therein. Thedistal end of each discharge column of the sample purification tray canbe in fluid communication with a respective receiving well of thereceiving well array. The sample tray heater module, according tovarious embodiments, can be disposed between the sample purificationtray and the receiving well array. The purification apparatus can belocated in a carriage such that the sample purification tray is capableof horizontal and/or vertical movement with respect to the heatingdevice and/or the receiving well array. Further details regardingexemplary sample purification trays, receiving well arrays, andpurification apparatuses, and methods for the use thereof, are describedin co-pending U.S. patent application Ser. No. 10/104,335, filed Mar.22, 2002.

[0028] According to various embodiments, a sample tray heater module isprovided that can include a heat distribution plate having a pluralityof protrusions, and a heat source. The heat source can be in contactwith a side of a bottom portion of the heat distribution plate. Thesample tray heater module can include a plurality of through holes fornozzle tips passing through the heat distribution plate and the heatsource.

[0029] The sample tray heater module can include a heating tray forholding the heat source and the heat distribution plate. The heatingtray can be capable of receiving and aligning the heat source and heatdistribution plate, and can include a plurality of through holes fornozzle tips corresponding to the through holes for nozzle tips in theheat distribution plate and the heat source. The heater module can beconstructed from a thermally conductive material, for example, a metalsuch as aluminum or stainless steel, a thermally conductive polymer, ora combination thereof.

[0030] According to various embodiments, and as shown in FIGS. 1-3, theheater module 10 can comprise a heat distribution plate 20 having abottom portion 22 having a first side and a second opposing side, andfrom which sidewalls 24 extend substantially perpendicularly orperpendicularly from the first side of bottom portion 22. Also extendingfrom the first side of bottom portion 22 can be a plurality ofprotrusions 26. As used herein, “protrusion” refers to a projection,extension, elongation, or other raised feature extending out of a planeof bottom portion 22. The sidewalls 24 and each of the plurality ofprotrusions 26 can be the same height. The plurality of protrusions 26and sidewalls 24 define a plurality of discharge column receptacles 28,for example, to accommodate a plurality of discharge conduits or columnsfrom a discharge conduit array, for example, a sample purification tray80. Each discharge column receptacle 28 can have a respective throughhole 30 for a nozzle tip through which a discharge column nozzle tip canextend. The heat distribution plate 20 can include screw-through holes32 as shown, tap holes, clips, or other devices useful for fastening theheater module together.

[0031] As shown in FIGS. 1 and 4-7, a heat source 40 can be in contactwith the second side of the bottom portion of the heat distributionplate 20. According to various embodiments, the heat source 40 can be asubstantially flat material. The heat source 40 can include a bottomlayer 44 in which can be disposed heating wires 50 for carrying power toa wire layout 48. The wire layout 48 can be attached to temperaturesensor wires or contact wires 52. According to various embodiments, andas shown in FIG. 1, the temperature probes 52 and/or the wires 50 canextend through through holes 94 of sample purification tray 80 to securethe sample purification tray 80 to the heater module 10. For example,the temperature sensor can be a thermistor or a thermocouple, or theheating wires themselves can act as temperature sensors as, for example,measured based on resistivity through the wires. The bottom layer 44 ofheat source 40 having the wire layout 48 disposed therein can be coveredby cover layer 46 to protect the wires. The heat source 40 can havethrough holes 54 for nozzle tips to extend therethrough. The throughholes 54 for nozzle tips can correspond to through holes 30 for nozzletips of a heat distribution plate 10 and, optionally, can correspond tothrough holes 66 for nozzle tips of a tray 60. The power wires 50 can beconnected to a controller 57 or connection module 56 as shown in FIGS. 7and 8. The controller 57 can be connected to a power source to provideenergy for heating the wires. The controller can include computercontrols, thermal cut-offs, and/or PID controllers, or other controllersthat can modify the current flowing through the heating elements and/orheating wires. The heat source 40 can be attached to or separate fromthe heat distribution plate 20. According to various embodiments, theheat source 40 can be incorporated in the heat distribution plate, forexample, by integral molding therewith. The heat source 40 can be incontact with the first side of the bottom portion 22 of the heatdistribution plate 20, wherein the first side of the bottom portion 22includes the surfaces of the plurality of protrusions 26.

[0032] As shown in FIGS. 7, 8, and 9, the heater module 10 can furthercomprise a tray 60 having an inwardly facing bottom portion 62 from afirst side of which sidewalls 64 extend substantially perpendicularly orperpendicularly. The tray 60 can be adapted to receive the heat source40 and the heat distribution plate 20 within the area defined bysidewalls 64 and bottom portion 62. The tray 60 can have through holes66 for nozzle tips corresponding to through holes 54 for nozzle tips ofthe heat source 40 and through holes 30 for nozzle tips of the heatdistribution plate 20. Tray 60 can also comprise screw holes 68 forfastening together the heater module by screws, bolts, or otherattachment devices passing through at least one screw-through hole 32and at least one screw hole 68.

[0033] The heat distribution plate 20 can be capable of receiving adischarge conduit array, for example, a sample purification tray 80, asshown in FIGS. 1 and 8. Sample purification tray 80 can include a topplate 82 from a side of which sidewalls 84 extend substantiallyperpendicularly or perpendicularly. Sample purification tray 80 can haveopenings 86 in top plate 82, which openings lead into discharge columns88. The discharge columns 88 can include more than one section, forexample, a first portion 90 and a second portion 92, as shown in FIGS. 1and 8. The discharge column 88 can terminate in a nozzle tip having adischarge opening 96 which is capable of fluid communication with arespective opening 106 in corresponding sample well tray or receivingwell array 100, as shown in FIG. 8. At least the nozzle tips ofdischarge columns 88 can pass through respective through holes 30 fornozzle tips of the heat distribution plate, respective through holes 54for nozzle tips of the heat source, and, optionally, respective throughholes 66 for nozzle tips of the tray 60, to extend below heater module10. The sample purification tray 80 can also have openings 94 to receivetemperature probe 52 and/or power wires 50 from heat source 40.

[0034] The portions 90, 92 of the discharge columns 88 of the samplepurification tray 80 can be formed separately and joined together by anysuitable method, such as heat welding or adhesive bond, or they can beintegrally formed such as by molding. Various methods of forming thesample purification tray will be apparent to those skilled in the art.The sample purification tray can be formed from a plastic material, ametal, or any other suitable material or combination of materials asknown to those skilled in the art. The sample purification tray can beformed of a material which does not interact or react with the sample tobe purified. Examples of suitable materials include polypropylene,polyethylene, polycarbonate, and mixtures thereof.

[0035] The sample purification tray 80 can be adapted to receive one ormore filters in one or more of the discharge columns 88. Various samplepurification trays and details regarding the size, shape, material, andmanufacture of sample purification trays, discharge conduit arrays, andfilters for use therein, can be found in co-pending U.S. patentapplication Ser. No. 10/104,335, U.S. Pat. No. 6,419,827 B1, and U.S.Pat. No. 6,159,368, all of which are herein incorporated in theirentireties by reference.

[0036] The sample purification tray can fit snuggly into heatdistribution plate 20 such that discharge columns 88 are in good, snug,thermal contact with the protrusions of heat distribution plate 20. Theregions between adjacent projections are referred to herein as dischargecolumn receptacles 28. According to various embodiments, a portion of atleast one of the plurality of protrusions 26 separates each dischargecolumn 88 from the next discharge column 88. According to variousembodiments, at least a portion of a discharge column 88 can be locatedbetween one of the plurality of protrusions 26 and a sidewall 24.

[0037] The sample purification tray and heater module can be held inhousing assembly 120 by carriage frame 122 having receiving area 124, asshown in FIG. 10.

[0038] According to various embodiments, and as shown and described inU.S. patent application Ser. No. 09/552,301, filed Apr. 18, 2000, andissued as U.S. Pat. No. 6,419,827 B1, which is incorporated herein inits entirety by reference, a vent plate can be located between theheater module 10 and the receiving well array 100. The vent plate canhave a plurality of though holes for nozzle tips corresponding to thethough holes for nozzle tips in the heater module, and corresponding tothe wells in the receiving well array, to allow fluid communication fromthe sample purification tray through the heater module and vent plate tothe receiving well array. Apertures or vents can extend through the ventplate. At least one aperture can be located adjacent each through holefor a nozzle tip in the vent plate. The apertures permit fluidcommunication between the regions above and below the vent plate. Bythis construction, a vacuum drawn from beneath the vent plate willextend to the regions above the vent plate. The vent plate material canbe the same as the material used to form the heater module.

[0039] According to various embodiments, an aerosol guard or othercross-flow restrictor, as described, for example, in U.S. patentapplication Ser. No. 09/182,946, filed Oct. 29, 1998, issued as U.S.Pat. No. 6,159,368, can be located between heater module 10 and ventplate 70, or between heater module 10 and sample well tray 100. Theaerosol guard can prevent aerosols from each of sample wells 108 fromcross-contaminating other sample wells. The aerosol guard can allow thepassage of gases, but not aerosols, therethrough. The aerosol guard canbe placed immediately adjacent and below heat source 40 of heater module10 or, if tray 60 is used, immediately adjacent and below tray 60 ofheater module 10. According to various embodiments, the aerosol guardcan be placed immediately adjacent and below a vent plate. The aerosolguard can include a plurality of through holes for nozzle tipspositioned substantially in alignment with one or more of through holes54 for nozzle tips of heat source 40, through holes 66 for nozzle tipsof tray 60, and through holes 72 for nozzle tips of heat plate 70, andalso substantially in alignment with openings 106 in top plate 102 ofsample well tray 100. At least the nozzle tips of discharge columns 88can pass through the through holes for nozzle tips of the aerosol guardand can be in fluid communication with sample wells 108 through openings106 of the sample well tray 100. The aerosol guard can be made of aflexible or non-flexible material and the material can be capable ofwithstanding the temperatures associated with use of heater module 10.The aerosol guard material can be substantially non-reactive with thechemicals and/or biological components of the sample. The aerosol guardcan be made from foam-like material. The aerosol guard can be a porous,hydrophilic polymer material, such as, for example, ethyl vinyl acetate.Other suitable materials for the aerosol guard are apparent to those ofordinary skill in the art.

[0040] Various embodiments and details of the vent plate and aerosolguard can be found in related co-pending U.S. patent application Ser.No. 10/104,335, U.S. Pat. No. 6,419,827 B1, and U.S. Pat. No. 6,159,368,all of which are incorporated herein in their entireties by reference.

[0041] As shown, for example, in FIG. 8, when the sample purificationtray 80 is fitted with heater module 10, at least the nozzle tips of thedischarge columns 88 can protrude through discharge column receptacles28 and through holes 30 for nozzle tips in heat distribution plate 20,through through holes 54 for nozzle tips in heat source 40, and,optionally, if tray 60 is used, through through holes 66 for nozzle tipsin tray 60, to extend below tray 60 or heat source 40 and be in fluidcommunication with sample well tray 100. According to variousembodiments, any sample placed in sample purification tray 80 through anopening 86 into a discharge column 88 can flow through the dischargecolumn 88 and can emerge from respective discharge opening 96 intorespective opening 106 of the top plate 102 of the sample well tray 100,and can proceed through opening 106 into respective sample well 108.According to various embodiments, the number of discharge columns 88,discharge openings 96, through holes 30, 54 and 66 for nozzle tips, andopenings 106 in sample well tray 100 are equivalent. According tovarious embodiments, the number of openings 106 in sample well tray 100can be less than the number of discharge columns 88, discharge openings96, and through holes 30, 54, and 66 for nozzle tips, such that multipleadjacent discharge columns 88 and corresponding discharge openings 96are in fluid communication with a single opening 106 of sample well tray100.

[0042] Heater module 10 is capable of providing heat to samplepurification tray 80 such that samples can be heated before and/orduring passage through discharge columns 88 of sample purification tray80. Heater module 10 can be, for example, capable of maintaining atemperature or raising a temperature of samples in the respectiveplurality of discharge columns 88 of sample purification tray 80 duringthe period of time it takes for the samples to pass through thedischarge columns 88.

[0043] According to various embodiments, heater module 10 is capable ofheating at a rate sufficient to heat 1 ml of water at 1° C. per minuteor greater, when the water disposed in a thermally conductive polymericreceptacle having an area of about three cm² in thermal contact with theheater module. For example, as shown in FIG. 11, the heater module 10can raise the temperature of 1 ml of water in a 0.25 inch diametercolumn of a sample purification tray 80 fitted into the heater module10, from about 23° C. to about 65° C. in 20 minutes or less. The heatermodule 10 can be capable of providing heat sufficient to heat samples toa temperature in a range of from about 5° C. to about 100° C. The heatermodule 10 can be capable of providing heat sufficient to heat samples toa temperature in a range of from about 20° C. to about 70° C.

[0044] One or more of the heat distribution plate 20, heat source 40,and tray 60 of the heater module 10 can be constructed from athermoconductive material. According to various embodiments, each of theheat distribution plate 20, heat source 40, and tray 60 are made from athermoconductive material. The thermoconductive material can be ametallic thermoconductive material, such as aluminum, iron, tantalum,titanium, copper, or alloys thereof. The thermoconductive material canbe a thermoconductive polymeric material capable of withstandingtemperatures in the range or from about 5° C. to about 100° C. withoutdeforming, cracking or melting. The polymeric material can include athermoconductive filler material. The filler material can be one or moredifferent fillers selected from a carbon material, boron nitride, andmetallic materials, for example, aluminum, alumina, copper, magnesium,and brass, or a combination thereof.

[0045] According to various embodiments, heat distribution plate 20 canbe constructed of a substantially rigid, thermoconductive material.According to various embodiments, the plurality of protrusions 26 can bemade of the same material as sidewalls 24. The heat distribution plate20, including bottom portion 22, sidewalls 24, and the plurality ofprotrusions 26, can be made of a substantially unitary construction. Forexample, the heat distribution plate 20 can be molded or machined toinclude the plurality of protrusions 26 and the sidewalls 24. Accordingto various embodiments, the plurality of protrusions 26 can be formedseparately from bottom portion 22 and bonded thereto or otherwiseattached. The sidewalls 24 can be formed separately from bottom portion22 and bonded or otherwise attached thereto. Bonding of the plurality ofprotrusions 26 or sidewalls 24 to bottom portion 22 can be done by anyknown process, for example, bonding by epoxy or by a welding processsuch as heat welding or ultrasonic bonding or welding.

[0046] According to various embodiments, wherein the thermoconductivematerial of the heat distribution plate 20 is a polymer, the materialcan be a mixture of one or more polymers, one or more monomers, or ofone or more polymers with at least one thermoconductive filler material.According to various embodiments, the polymer can be a liquid crystalpolymer. According to various embodiments wherein a thermally conductivefiller material is used, the filler material can be one or moredifferent fillers selected from a carbon material, boron nitride, andmetallic materials, for example, aluminum, alumina, copper, magnesium,and brass, or a combination thereof. Various examples of thermallyconductive composite materials are described, for example, in U.S. Pat.No. 6,048,919. Exemplary thermally conductive liquid crystallinepolymers (LCP) can be obtained from Cool-Polymers, Inc. under thetrademarks Cool-Poly® E200, Cool-Poly® RB018, Cool-Poly® RB019,Cool-Poly® RB020, Cool-Poly® RS008, Cool-Poly® D2, Cool-Poly® RS007, andCool-Poly® RS012.

[0047] According to various embodiments wherein a tray 60 is part of theheater module 10, the tray 60 can be made of or include anythermoconductive material as described herein. According to variousembodiments, the tray 60 can be made from the same material as the heatdistribution plate 20, for example, the same thermoconductive material.According to various embodiments, the heating tray can be anon-conductive material. The heating tray can be made of glass, ceramic,a polymeric material, a metal, an alloy, or a combination thereof.According to various embodiments wherein a tray 60 is included, the heat40 source can be located against bottom portion 62 of tray 60 in a spacedefined by bottom portion 62 and sidewall 64. The heat source 40 can bebonded to or placed against bottom portion 62 of tray 60. The heatsource 40 can be bonded or otherwise attached to a side of the bottomportion 22 of heat distribution plate 20, which can be set into tray 60in a space defined by bottom portion 62 and sidewall 64. According tovarious embodiments, both a heat distribution plate 20 and a tray 60 canbe used in a heater module 10 wherein both the heat distribution plate20 and tray 60 can be made of or include aluminum. The heater module 10can contain both a heat distribution plate 20 and a tray 60, wherein theheat distribution plate 20 and tray 60 can both be made of or include athermoplastic material. According to various embodiments wherein theheat distribution plate 20 and tray 60 are both made from or includethermoplastic material, the heat distribution plate 20 and tray 60 canbe bonded together. Heat distribution plate 20 and tray 60 can be bondedtogether after, for example, placing a heat source 40 between the heatdistribution plate 20 and tray 60. Such bonding can be achieved by anymethod known to those skilled in the art, such as by the use of epoxy,thermoconductive epoxy, or thermal bonding. According to various otherembodiments, the heat distribution plate 20 and tray 60 can be attachedmechanically such that the heater module 10 comprising the heatdistribution plate 20 and tray 60 with or without a heat source 40therebetween can be moved as a single unit.

[0048] According to various embodiments, the heat source 40 can includeany heating system known to those skilled in the art to provide uniformdistribution of heat. The heat source 40 can be attached to the heatdistribution plate 20, attached to the tray 60, attached to both theheat distribution plate 20 and tray 60, or set between the heatdistribution plate 20 and tray 60. The heat source 40 can be made from aflexible material and can comprise a film or sheet, for example, apolyimide sheet material such as KAPTON, available from DuPont HighPerformance Materials, Circleville, Ohio. The heat source 40 can be aprinted resistor circuit on a side of bottom portion 22 of heatdistribution plate 20 or can be a printed resistor circuit on the bottomportion 62 of tray 60, wherein the printed resistor circuit is capableof generating heat. According to various embodiments wherein the heatsource 40 comprises a printed resistor circuit in the form of wirelayout 48, the wire layout 48 can be made from any conductive materialcapable of producing a predetermined, minimum, and/or maximum amount ofheat. For example, the wire layout can be made from various metals ormetal alloys, including gold, silver, aluminum, copper, titanium, alloysthereof, and other metals and metal alloys as known to those of ordinaryskill in the art. The wire layout 48 can be set forth in a bottom layer44 capable of accepting and holding in place the wire layout. The bottomlayer 44 can be made from a flexible or nonflexible material. The bottomlayer 44 can be made from silicone, a polymeric material, glass, or anyother material known to those of ordinary skill in the art, includingcomposite materials. The cover layer 46 can be made of or include anymaterial capable of encapsulating wire layout 48 and bottom layer 44,wherein the cover layer material is capable of transferring heat fromthe wire layout 48 to the heat distribution plate 20. According tovarious embodiments, the cover layer 46 can be the same material as thebottom layer 44. According to various embodiments, the cover layer 46can be a polymeric material. Other suitable materials are apparent tothose of ordinary skill in the art.

[0049] The heat source 40 comprising the bottom layer 44, wire layout48, and cover layer 46, can be capable of generating a predeterminedamount of heat dependent upon the resistance and current input of thewire layout 48. The amount of heat capable of being generated can bechanged by changing the resistance of wire layout 48, or by lowering orraising the amount of current passing through wire layout 48. Electricalcurrent is provided to wire layout 48 through wires 50, which areconnected to controller 57 by connector 56. Controller 57 can controlthe amount of current that passes through wires 50 to wire layout 48,and therefore the amount of heat generated by wire layout 48 and heatsource 40.

[0050] According to various embodiments, heat source 40 can be formedintegrally with tray 60 or heat distribution plate 20. The heat source40 can be formed integrally with tray 60 such that bottom layer 44 ofheat source 40 corresponds to bottom portion 62 of tray 60. The heatsource 40 can be formed integrally with heat distribution plate 20 suchthat cover layer 46 of heat source 40 corresponds to bottom portion 22of heat distribution plate 20.

[0051] According to various embodiments, a heat source can beincorporated into heat distribution plate 20. In such embodiments, heatdistribution plate 20 with the incorporated heat source can be used asan alternative to or in addition to heat source 40. Wires, a wirelayout, and/or a printed resistor circuit can be molded or otherwiseformed within the heat distribution plate 20 having an incorporated heatsource. The wires, wire layout, and/or printed resistor circuit can bemolded or otherwise formed within at least one of the bottom portion 22,the sidewalls 24, and the plurality of protrusions 26. The heatdistribution plate 20 with the incorporated heat source can be formedsimilar to the way that a steel-reinforced concrete slab is formed bypouring concrete into a mold containing a network or a grid pattern ofsteel rebar. For example, at least part of a network of resistors,wires, a wire layout, resistive heat elements, and/or a printed resistorcircuit can be placed into a mold and a thermoconductive material thatis in a molten state can be poured into the mold. When thethermoconductive material hardens, the hardened object forms the heatdistribution plate 20 with the incorporated heat source. The resistors,wires, wire layout, resistive heat elements, and/or printed resistorcircuit can be affixed to, inserted in, and/or embedded into the atleast one of the bottom portion 22, the sidewalls 24, and the pluralityof protrusions 26. The resistors, wires, wire layout, resistive heatelements, and/or printed resistor circuit can be made of various metalsor metal alloys, including gold, silver, aluminum, copper, titanium,alloys thereof, and other metals and metal alloys as known to those ofordinary skill in the art. The heat distribution plate 20 with theincorporated heat source can be capable of generating a predeterminedamount of heat dependent upon the resistance and current input of thewires and/or wire layout. A controller can provide current to the wiresand/or wire layout via a connector. The heat distribution plate 20 withthe incorporated heat source can perform in the same manner as the heatsource 20 without the incorporated heat source and heat source 40.

[0052] According to various embodiments, the temperature of the sampletray heater module 10 can be monitored. The heat source 40 can includeone or more heat sensor or temperature probe 52 such as a thermistor, athermostat, a thermal protection tube, or a non-contact sensor such asan infrared sensor. The heat sensor or temperature probe 52 can bepositioned such that it contacts the bottom portion 22 of heatdistribution plate 20. The heat generated by heat source 40 can becontrolled based upon the temperature detected or temperature readingsobtained from the heat sensor or temperature probe 52. Other suitableheat sensors or temperature probe designs as known to those of ordinaryskill in the art can be used with heat source 40. For example, the heatsensor or temperature probe can be located above sample purificationtray 80 in order to determine the temperature of the samples insidedischarge columns 88. According to various embodiments, a heat sensor ortemperature probe can be located inside one or more of the dischargecolumns 88.

[0053] According to various embodiments, and as shown in FIG. 1, heatermodule 10 is designed to interact with and complement samplepurification tray 80. The sidewalls 24 of heat distribution plate 20 ofheater module 10 extend substantially perpendicularly or perpendicularlyfrom a side of bottom portion 22 such that when mated with a samplepurification tray 80, the sidewalls 24 of heat distribution plate 20substantially cover discharge columns 88 of sample purification tray 80from view. According to various embodiments, the sidewalls 24 of heatdistribution plate 20 can touch a side of top plate 82 of the samplepurification tray 80. According to various other embodiments, thesidewalls 24 of heat distribution plate 20 can be in contact with one ormore discharge columns 88 of sample purification tray 80. The sidewalls24 can be in contact with one or more portion of discharge column 88,for example, the second portion 92 or the first portion 90 of dischargecolumn 88. According to various other embodiments, the sidewalls 24 ofheat distribution plate 20 can be in contact with the sidewalls 84 ofthe sample purification tray 80. The plurality of protrusions 26 of heatdistribution plate 20 can be in contact with a side of top plate 82 ofthe sample purification tray 80. According to various embodiments, theplurality of protrusions 26 of heat distribution plate 20 extend fromheat distribution plate 20 and are located between discharge columns 88of the sample purification tray 80. According to various embodiments,each of the plurality of protrusions 26 is in contact with one or moreof the discharge columns 88. For example, one or more of the pluralityof protrusions 26 can be in contact with a second portion 92, a firstportion 90, or both a second portion 92 and a first portion 90, of adischarge column 88 of sample purification tray 80. At least a portionof one or more of the discharge columns 88 can substantially fit betweentwo or more of the plurality of protrusions 26, or between one or moreof the plurality of protrusions 26 and sidewall 24 of the heatdistribution plate 20.

[0054] According to various embodiments, the plurality of protrusions 26of the heat distribution plate 20 can function as a heat sink todissipate heat by heating discharge columns 88 of the samplepurification tray 80. A fan can be positioned to promote heatdistribution between the plurality of protrusions 26 and heat absorptionby the discharge columns 88.

[0055] According to various embodiments, one or more of through hole 30for a nozzle tip of heat distribution plate 20, through hole 54 for anozzle tip of heat source 40, and optionally through hole 66 for anozzle tip of tray 60, can be sized so as to closely fit the profile ofdischarge column 88 of sample purification tray 80. One or more throughhole 30, 54, or 66 for a nozzle tip can be sized to closely mate with acorresponding discharge column 88 so that bending of the dischargecolumn 88 can be minimized. According to various embodiments, thespacing of one or more through hole 30, 54, or 66 for a nozzle tip, canassist in maintaining equal spacing between the discharge columns 88.

[0056] According to various embodiments, a purification apparatuscomprising a sample purification tray 80, a heater module 10, a samplewell tray 100, optionally a vent plate, and optionally an aerosol guard,can be formed using the components described herein. For purification ofa sample, the purification apparatus can be placed under vacuumconditions to create a pressure differential. According to variousembodiments wherein a vacuum condition will be endured, openings andseams in the purification apparatus, and between the purificationapparatus and a housing assembly 120, can be sealed using any sealantcapable of maintaining vacuum conditions as known to those of ordinaryskill in the art. An exemplary sealant can be made fromorganopolysiloxane materials. Other suitable sealants as known to thoseof ordinary skill in the art can be used such as those described, forexample, in U.S. Pat. Nos. 5,929,138; 5,079,300; 5,037,667; 4,950,546;4,777,063; 4,680,233; and 4,595,635.

[0057] A purification apparatus as described herein can be used forfiltering samples, such as biological materials, and directing thefiltered samples into a plurality of respective sample wells in a samplewell tray or receiving well array. Any procedure known to those ofordinary skill in the art can be used to filter the samples. Forexample, purification of a nucleic acid such as RNA for polymerase chainreaction (PCR) analysis can be performed using the purificationapparatus set forth herein. Besides RNA purification, other processessuch as, but not limited to, purification of DNA, extraction and/orpurification of RNA or DNA from blood, and extraction and/orpurification of proteins, can be performed using the purificationapparatus described herein. The purification apparatus can be used forpurifying specific sequences of DNA or RNA by varying, for example, thefilter element of the sample purification tray, the chemistries used toreact with the sequences, and/or reagents. The purification apparatuscan be used for processing biological or chemical samples, such as byfiltration, separation, species immobilization, or other chemical orphysical action or reaction of two or more chemical or biologicalsubstances.

[0058] Various purification, filtration, separation, immobilization, orreaction processes can be enhanced by heating during processing. Thepurification apparatus as described herein can be heated duringprocessing of samples. The ability to heat a sample tray of apurification apparatus as described herein allows the apparatus to beused for a wide range of processes. Heating can increase the kineticenergy of the samples in the discharge columns of the samplepurification tray, which can result in a decrease in the amount of timerequired for reaction, facilitate a more thorough mixing of the sample,catalyze a reaction, and/or lower viscosity to facilitate discharge ofthe sample through the filtering medium. Maintaining the temperature ofa sample during filtering, purification, separation, immobilization, orreaction can improve or maintain viability of the sample, and/ordecrease reaction times of later process steps. According to variousembodiments, the use of a heater module as described herein in apurification apparatus can avoid or eliminate compatibility issues ofbiological samples, such as PCR material, by indirectly heating thesamples of such materials and not directly heating the samplesthemselves. The purification apparatus described herein can be used tomaintain a constant temperature, or to fluctuate the temperature of asample during processing.

[0059] The purification apparatus as described herein can be used, forexample, in manual or automated workstations for sample preparations.For example, one or more of the sample purification tray, heater moduleand sample well tray of various embodiments can be used in the ABI PRISM6700 Automated Nucleic Acid Workstation or the ABI PRISM 6100Workstation, both of which are manufactured by Applied Biosystems. Oneor more of the sample purification tray, heater module, and sample welltray can also be suitable for use with a wide variety of availableautomated or manual sample preparation workstations, which workstationsare known to those of ordinary skill in the art.

[0060] According to various embodiments, the heater module describedherein can be used to heat a sample purification tray while the samplepurification tray is being installed in a housing assembly.Interrelation of a sample purification tray and carriage frame of ahousing assembly is set forth, for example, in U.S. Pat. No. 6,419,827B1, incorporated herein in its entirety by reference.

[0061] According to various embodiments, one or more samples can beplaced in one or more of the plurality of discharge columns 88 of asample purification tray 80 such that the samples pass through thedischarge columns 88, through respective discharge openings 96, and intorespective openings 106 of sample wells 108 of a sample well tray 100.The samples can be heated by heater module 10 while they are passedthrough discharge columns 88. The heat distribution plate 20 of heatermodule 10 can surround and provide constant and uniform heating to eachof the plurality of the discharge columns 88 and thereby uniformly heatthe sample or samples passing through the discharge columns 88. Theheater module 10 can be used to preheat the sample purification tray 80,to heat the sample purification tray 80 while a sample passestherethrough, or to preheat and heat the sample purification tray 80during use.

[0062] Various examples of the components described herein are furtherset forth and described, for example, in co-pending related U.S. patentapplication Ser. No. 10/104,335, U.S. Pat. No. 6,419,827 B1, and U.S.Pat. No. 6,159,368. All publications cited herein are incorporated byreference in their entireties.

[0063] Those skilled in the art can appreciate from the foregoingdescription that the broad teachings of the present invention can beimplemented in a variety of forms. Therefore, while this invention hasbeen described in connection with certain embodiments and examplesthereof, the true scope of the invention should not be so limited.Various changes and modifications can be made without departing from thescope or spirit of the invention, as defined by the appended claims.

What is claimed is:
 1. A heater module comprising: a heat distributionplate comprising a bottom portion having a first side and an oppositesecond side, a plurality of protrusions spaced from one another andextending away from the first side, and a plurality of through holespassing through the heat distribution plate; and a heat source inthermal contact with the heat distribution plate and comprising athermally conductive material capable of providing uniform heatingacross the heat distribution plate, the heat source including aplurality of through holes; wherein the plurality of through holesthrough the heat distribution plate are aligned with the plurality ofthrough holes through the heat source.
 2. The heater module of claim 1,wherein the heat distribution plate further comprises sidewallsextending away from the first side.
 3. The heater module of claim 2,wherein each of the plurality of protrusions has a distal tip and aheight equal to the distance the distal tip extends away from the firstside of the heat distribution plate, and wherein the sidewalls each havea height equal to the distance the sidewalls extends away from the firstside of the heat distribution plate, and wherein the height of theprotrusions are equal to the height of the sidewalls.
 4. The heatermodule of claim 1, wherein the heat source is incorporated in the heatdistribution plate.
 5. The heater module of claim 1, wherein the heatsource comprises a first side.
 6. The heater module of claim 5, whereinthe first side of the heat source is in contact with the first side ofthe heat distribution plate.
 7. The heater module of claim 5, whereinthe first side of the heat source is in contact with the second side ofthe heat distribution plate.
 8. The heater module of claim 1, furthercomprising a heating tray including an inwardly facing bottom surfaceand sidewalls extending away from the bottom surface, wherein theheating tray is adapted to receive both the heat distribution plate andthe heat source.
 9. The heater module of claim 8, wherein the heatingtray further comprises a plurality of through holes capable of beingaligned with the pluralities of through holes through the heatdistribution plate and through the heat source.
 10. The heater module ofclaim 8, wherein the heat distribution plate is disposed within theheating tray, and the heat source is disposed within the heating traybetween the bottom surface of the heating tray and the heat distributionplate.
 11. The heater module of claim 1, wherein the heat source furthercomprises a temperature sensor.
 12. The heater module of claim 1,wherein the heat distribution plate comprises a polymeric material. 13.The heater module of claim 1, wherein the heat distribution platecomprises a metallic material.
 14. The heater module of claim 13,wherein the metallic material is selected from aluminum, copper,titanium, tantalum, iron, alloys thereof, and combinations thereof. 15.The heater module of claim 8, wherein the heating tray comprises ametallic material.
 16. The heater module of claim 15, wherein themetallic material is selected from aluminum, copper, titanium, tantalum,iron, alloys thereof, and combinations thereof.
 17. The heater module ofclaim 8, wherein the heating tray comprises a polymeric material. 18.The heater module of claim 8, wherein the heating tray comprises athermoconductive material.
 19. The heater module of claim 8, wherein theheating tray comprises a non-thermoconductive material.
 20. The heatermodule of claim 1, wherein at least some of the through holes aresurrounded by two or more of the protrusions.
 21. A sample purificationapparatus comprising: a heater module of claim 1; and a samplepurification tray comprising a first surface, a second surface opposingthe first surface, and a plurality of purification columns extendingaway from the second surface, each purification column including adistal tip portion including an outlet opening through which sampleliquid in the purification column can be discharged from thepurification column, wherein the plurality of purification columns arespaced from one another in an array having a configuration adapted suchthat the purification columns can be positioned among the plurality ofprotrusions of the heat distribution plate so that at least some of theplurality of discharge columns are each surrounded by two or morerespective protrusions of the plurality of protrusions, and such thatthe outlet openings of the plurality of purification columns are capableof being aligned with the plurality of through holes through the heatdistribution plate.
 22. The purification apparatus of claim 21, whereinthe heater module further comprises sidewalls extending away from thefirst surface.
 23. The purification apparatus of claim 21, wherein thesample purification tray engages the heater module such that at leastone of the protrusions of the heat distribution plate is surrounded byfour purification columns.
 24. The purification apparatus of claim 21,wherein the sample purification tray engages the heater module such thatat least one of the purification columns of the sample purification trayis surrounded by four of the protrusions of the heat distribution plate.25. The purification apparatus of claim 21, wherein the samplepurification tray is in mating engagement with the heater module suchthat the plurality of purification columns abut the plurality ofprotrusions.
 26. A purification method comprising: providing the samplepurification apparatus of claim 17; disposing a plurality of respectivesamples in the purification columns of the sample purification tray;activating the heat source of the heater module to provide heat to theheat distribution plate; and passing the samples through thepurification columns and out the respective outlet openings while theheat distribution plate heats the samples.
 27. The method of claim 26,comprising heating the respective samples to a temperature of from about20° C. to about 70° C.
 28. The method of claim 26, comprising heatingthe respective samples at a rate of about 1° C. per minute or greater.29. The method of claim 26, wherein the heat source of the heater moduleis activated before the plurality of respective samples is disposed inthe purification columns of the sample purification tray.